Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “RELAXATION”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 37 records · Page 2Linked to original sources
PubMed1987

Endothelium-derived relaxing factor is a selective relaxant of vascular smooth muscle.

The present study examines the relaxant selectivity of endothelium-derived relaxing factor (EDRF) released from cultured endothelial cells. Endothelial cells from bovine pulmonary artery (CCL-209) in culture were grown on Cytodex-3 microcarrier beads, packed into a column and superfused to release EDRF. EDRF response was estimated by its ability to relax phenylephrine-contracted rings of rabbit aorta. Bradykinin and A23187 (10(-10) to 10(-6) M) caused dose-dependent release of EDRF from cultured bovine pulmonary artery endothelial cells. The release was dependent on endothelial cell number. A23187 caused a larger and longer-lasting release of EDRF than bradykinin. EDRF relaxation was selective for blood vessels. EDRF relaxed rabbit aortic rings, but it did not relax histamine-contracted guinea pig tracheal, rabbit taenia coli strips or oxytocin-contracted guinea pig uterine rings. These nonvascular smooth muscles were, however, relaxed by isoproterenol (10(-4) M) and sodium nitroprusside (SNP, 10(-5) M). The sensitivity of guinea pig aortic rings and tracheal strips to SNP were compared. The IC50 values for SNP (10(-9) to 10(-5) M) were 0.07 and 0.3 microM for aortic rings and tracheal strips, respectively. Although the tracheal strips were about 4-fold less sensitive than the aorta toward SNP, a complete relaxation was achieved. These results suggest that EDRF relaxes vascular smooth muscles but not respiratory, Gl or reproductive smooth muscles. Thus, EDRF may be a selective relaxant of vascular smooth muscle.

Animals↗
PubMed1996

Magnetization exchange in capillaries by microcirculation affects diffusion-controlled spin-relaxation: a model which describes the effect of perfusion on relaxation enhancement by intravascular contrast agents.

The effect of perfusion on relaxation time in tissue has only been considered for first-pass kinetics of NMR-signal after application of contrast agents. The importance of perfusion on relaxation has not yet been studied for steady state conditions, i.e., when the intravascular relaxation rate is constant in time. The aim of this study is to develop a model in which T1 relaxation is derived as a function of perfusion and intracapillary volume fraction (regional blood volume). Tissue is considered to be two-compartment system, which consists of intracapillary and extravascular space. Intracapillary relaxation differs from relaxation in the arterial system due to diffusion-exchange of magnetization from extravascular to intracapillary space. Perfusion tends to attenuate this difference and thus counteracts the effect on intracapillary relaxation. Relaxation in the extravascular and intracapillary magnetization are linked by diffusion. This dependence is presented in analytical form and a generic equation is derived. AT1 experiment is considered in which all spins of tissue and blood are inverted at the beginning. Calculations are performed for the fast exchange model of tissue. Perfusion increases relaxation enhancement of intravascular contrast agents. This effect is considerable in highly perfused tissue like myocardium. The dependence of relaxation on perfusion implies an overestimation of the regional blood volume when the calculation of the latter is based on tissue models that neglect perfusion. The model presented here is applied to predict the effect of perfusion on T1 imaging with FLASH-pulse sequences because this technique has been proven to be a powerful method to obtain T1 maps within a short time interval. For the fast exchange model, two algorithms are suggested that determine perfusion and regional blood volume from T1 imaging in the presence and absence of intravascular contrast agents.

Blood Volume↗
PubMed1996

A comparative study of endothelium-derived relaxing factor-mediated relaxation and smooth muscle cell function in arterial and venous vein bypass grafts.

The development of intimal hyperplasia in reversed vein grafts is associated with altered endothelial and vasomotor function. This study examines the effect of surgery on the morphology and vasomotor function of experimental arterial and venous vein bypass grafts. Twelve reversed vein grafts, 12 in situ vein grafts and 12 venovenous grafts were placed in 24 New Zealand White rabbits. All grafts remained patent and were harvested after 28 days. Isometric contraction to norepinephrine, histamine, bradykinin, serotonin and relaxation to acetylcholine and sodium nitroprusside following pre-contraction with prostaglandin F(2 alpha) were determined on the grafts and on contralateral jugular veins. Compared to the contralateral jugular veins, norepinephrine supersensitivity was induced in the reversed vein grafts, and venovenous vein grafts but not in the in situ vein grafts. Decrease in histamine sensitivity occurred in all grafted vessels. Bradykinin responses were significantly reduced in the in situ vein grafts and reversed vein grafts. Contractile responses to serotonin developed in the in situ vein grafts and reversed vein grafts only. Acetylcholine-induced endothelium-derived relaxing factor-mediated relaxation of the contralateral jugular veins was preserved in both venovenous grafts and in situ vein grafts but was lost in reversed vein grafts. All tissues relaxed to sodium nitroprusside in dose-dependent manner. The data suggest that norepinephrine supersensitivity in reversed vein grafts results from excision of the vessel. Attenuation of bradykinin responses and the enhanced contractile responses to serotonin appear predominantly to result from arterialization. Decreases in histamine sensitivity appear related both to excision and to arterialization. Neither the excision of the vein nor arterialization individually influences the alterations in endothelium-derived relaxing factor-mediated relaxation. However, a combination of excision and arterialization results in the altered endothelium-derived relaxing factor-mediated relaxation. This study suggests that the surgical preparation of the vein and the surgical procedure used have significantly different effects on endothelium-derived relaxing factor-mediated relaxation and smooth muscle contractility in vein grafts.

Acetylcholine↗
PubMed1999

Differentiation of abnormal relaxation pattern with aging from abnormal relaxation pattern with coronary artery disease in transmitral flow with the use of tissue Doppler imaging of the mitral annulus.

An abnormal relaxation pattern in transmitral flow velocity waveforms has been observed in older healthy subjects as well as in patients with heart disease. Accordingly, we investigated whether the hemodynamic differences between patients with coronary artery disease (CAD) with an abnormal relaxation pattern in transmitral flow (ratio of E-wave to A-wave velocities < 1.0) and healthy older subjects with an abnormal relaxation pattern can be distinguished with the use of mitral annular velocity (MAV) during early diastole. We measured MAV in the longitudinal direction of the heart during early diastole by M-mode color tissue Doppler imaging in 24 patients with atypical chest pain (defined as healthy subjects in this study) and 70 patients with CAD who underwent cardiac catheterization. In all patients a time constant of left ventricular pressure decay (tau) and the left ventricular (LV) end-systolic volume index were also measured. Twenty-one healthy subjects and 59 patients with CAD had an abnormal relaxation pattern in their transmitral flow. The age, heart rate, mean blood pressure, and ratio of E-wave to A-wave velocities were not different between the two groups. However, the tau was longer and the LV end-systolic volume index was greater in patients who had an abnormal relaxation pattern with CAD than in healthy subjects with an abnormal relaxation pattern. The MAV during early diastole was lower in the former than in the latter (5.8 +/- 1. 9 vs 9.8 +/- 1.9 cm/s, P <.001). Mitral annular velocity during early diastole by M-mode color tissue Doppler imaging can detect the differences in LV relaxation and LV systolic performance between the abnormal relaxation pattern with CAD and the physiologically abnormal relaxation pattern with aging, providing further information regarding the meaning of an LV abnormal relaxation pattern.

Aging↗
PubMed1992

Characterization of the receptor mediating relaxation to substance P in canine middle cerebral artery: no evidence for involvement of substance P in neurogenically mediated relaxation.

1. The aim of this study was to characterize the neurokinin receptor which mediates relaxation of dog isolated middle cerebral artery by the use of selective agonists and antagonists and to establish whether substance P is involved in the neurogenically mediated relaxant response in this vessel. 2. Substance P caused concentration-related, endothelium-dependent relaxations of dog isolated middle cerebral artery, contracted with prostaglandin F2 alpha. The selective NK1 receptor agonists, GR73632 and substance P methyl ester (SPOMe), also caused relaxation with similar maximum effects to those of substance P. GR73632 and SPOMe were approximately 20 times and 6 times less potent respectively than substance P. The selective NK2 and NK3 receptor agonists, GR64349 and senktide, were only weakly active in causing relaxation being at least 425 times and 245 times less potent respectively than substance P. 3. The selective NK1 receptor antagonist, GR82334, was a potent, specific, competitive antagonist of the relaxant effects of substance P. In contrast, the selective NK2 receptor antagonist, R396 (10 microM) had no effect on the response to substance P. 4. Electrical field stimulation of dog isolated middle cerebral artery, contracted with prostaglandin F2 alpha, caused neurogenically mediated, non-adrenergic non-cholinergic (NANC) relaxations. These NANC relaxations were unaffected by endothelium removal, GR82334 (10 microM) or by capsaicin (10 microM) treatment. However, the nitric oxide synthesis inhibitor, L-NG-monomethyl arginine methyl ester (L-NMMA) (100 microM) markedly attenuated the response to electrical stimulation. 5. These results suggest that substance P causes relaxation of dog isolated middle cerebral artery via activation of NK1 receptors. However, substance P does not appear to be involved in NANC neurotransmission. In contrast, the marked inhibitory effect of L-NMMA on NANC relaxations implicates nitric oxide in NANC neurotransmission in this vessel.

Animals↗
PubMed1988

Endothelium-derived relaxing factor and nitric oxide possess identical pharmacologic properties as relaxants of bovine arterial and venous smooth muscle.

The principal objective of this study was to compare and contrast the vascular smooth muscle-relaxing properties of endothelium-derived relaxing factor (EDRF) and nitric oxide (NO) in two different assay systems. In one system, precontracted rings of bovine intrapulmonary artery and vein and coronary artery were used to compare the relaxant effects of endothelium-dependent vasodilators, NO, S-nitroso-N-acetylpenicillamine, glyceryl trinitrate, prostacyclin and isoproterenol. In a second system, a bioassay superfusion cascade procedure was employed to compare the relaxant effects and biologic stability of EDRF and NO. Acetylcholine and bradykinin elicited concentration-dependent but transient relaxant responses in arterial and venous rings, respectively. NO and S-nitroso-N-acetylpenicillamine, which generates NO in solution, elicited similar transient relaxant responses in endothelium-denuded arterial and venous rings. Glyceryl trinitrate, however, produced sustained relaxations, as did isoproterenol and prostacyclin. Utilizing a bioassay superfusion cascade system in which intact perfused artery or vein was the source of EDRF and three endothelium-denuded arterial or venous strips mounted in series served as the detector of EDRF or NO, the relaxation profile and biologic stability of superfused EDRF were compared with those of superfused NO. Arterial or venous perfusion with acetylcholine or bradykinin, respectively, and superfusion of NO over the strips produced characteristic decremental relaxant responses in the three vascular strips and revealed the highly unstable nature of EDRF and NO (T1/2 = 3-5 sec for both). The relaxation profile of EDRF was indistinguishable from that of NO.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1980

A comparison of somatic relaxation and EEG activity in classical progressive relaxation and transcendental meditation.

Oxygen consumption, electroencephalogram (EEG), and four other measures of somatic relaxation were monitored in groups of long-term practitioners of classical Jacobson's progressive relaxation (PR) and Transcendental Meditation (TM) and also in a group of novice PR trainees. All subjects (1) practiced relaxation or meditation (treatment), (2) sat with eyes closed (EC control), and (3) read from a travel book during two identical sessions on different days. EEG findings indicated that all three groups remained primarily awake during treatment and EC control and that several subjects in each group displayed rare theta (5-7 Hz) waveforms. All three groups demonstrated similar decrements in somatic activity during treatment and EC control which were generally of small magnitude (e. g., 2-5% in oxygen consumption). These results supported the "relaxation response" model for state changes in somatic relaxation for techniques practiced under low levels of stress but not the claim that the relaxation response produced a hypometabolic state. Despite similar state effects, the long-term PR group manifested lower levels of somatic activity across all conditions compared to both novice PR and long-term TM groups. We concluded that PR causes a generalized trait of somatic relaxation which is manifested in a variety of settings and situations. Two likely explanations for this trait were discussed: (1) PR practitioners are taught to generalize relaxation to daily activities, and/or (2) according to a "multiprocess model," PR is a "somatic technique," which should produce greater somatic relaxation than does TM, a "cognitive technique." Further research is required to elucidate these possibilities.

Adult↗
PubMed1990

Comparison of relaxation responses of vascular and non-vascular smooth muscle to endothelium-derived relaxing factor (EDRF), acidified sodium nitrite (NO) and sodium nitroprusside.

Smooth muscle relaxant activity of endothelium-derived relaxing factor (EDRF) released from columns of cultured bovine endothelial cells by bradykinin (0.1-3 nmol/l) was measured in four non-vascular preparations: guinea-pig taenia caeci, guinea-pig trachea, rat stomach (fundus) and rat anococcygeus. Each preparation was contracted to a steady level of force with a variety of agonists such that they relaxed optimally to sodium nitroprusside (SNP). The EDRF-induced relaxations in each preparation were compared with those obtained in de-endothelialized ring preparations of greyhound coronary artery by means of paired bioassays run in parallel. EDRF released from the endothelial cell columns caused 80-100% relaxation of the coronary artery, 40-80% in the guinea-pig taenia caeci, 50-70% in the rat anococcygeus, 5-8% in the guinea-pig trachea and was undetectable in the rat stomach strip. By comparison, SNP caused maximal relaxation in all tissues compared with the coronary artery. In separate organ bath experiments the sensitivity to nitric oxide (NO: generated by adding acidified solutions of NaNO2) and SNP was compared in each preparation. SNP caused maximal relaxation in all tissues with the following order of potency: dog coronary artery greater than guinea-pig trachea greater than guinea-pig taenia = rat anococcygeus greater than rat stomach strip. In contrast, the concentration of acidified NaNO2 (NO, 300 nmol/l) that caused 96 +/- 4% relaxation in the dog coronary artery caused 84 +/- 7% and 48 +/- 1% relaxation in the taenia and anococcygeus respectively. No response attributable to NO was detected in either the trachea or rat stomach strip.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Smooth muscle relaxing effects of NO, nitrosothiols and a nerve-induced relaxing factor released in guinea-pig colon.

1. The aim of the present study was to compare the biological activity of S-nitroso-L-cysteine (CYSNO), S-nitrosoglutathione (GSNO), S-nitroso-N-acetyl-D,L-penicillamine (SNAP) and hydroxylamine to that of nitric oxide (NO) and a vascular relaxing factor released by nerve stimulation in the guinea-pig intestine. The biological activity was examined in a bioassay system with guinea-pig colon as donor tissue and a series of spiral strips of rabbit aorta without endothelium as detector tissues. 2. Electrical stimulation of the guinea-pig colon released a vascular relaxing factor. The half-life of the relaxing factor down the bioassay cascade was the same as exogenously applied NO. N omega-nitro-L-arginine (L-NOARG) inhibited the release of bioactivity. 3. The relaxations of the assay tissues caused by exogenous CYSNO also declined during the passage down the cascade. However, in the presence of L-cysteine (10(-5) M) the half-life of CYSNO increased and there was no significant breakdown through the cascade. In contrast, the half-life of applied NO and the vascular relaxing factor released by nerve stimulation was unaffected by the presence of L-cysteine. 4. Exogenously applied GSNO (20-50 nM), SNAP (2-4 nM) and hydroxylamine (300-600 nM) caused relaxations that did not decline during the passage down the cascade. 5. In summary, the relaxation of the bioassay tissues during nerve stimulation was indistinguishable from the relaxation induced by NO, whereas relaxations induced by CYSNO, GSNO, SNAP and hydroxylamine showed different pharmacological profiles. The released bioactivity is thus likely to be NO itself.

Animals↗
PubMed1995

Water mobility in poly(ethylene glycol)-, poly(vinylpyrrolidone)-, and gelatin-water systems, as indicated by dielectric relaxation time, spin-lattice relaxation time, and water activity.

The mobility of water molecules present in poly(ethylene glycol) (PEG)-, poly(vinylpyrrolidone) (PVP)-, and gelatin-water systems was determined by dielectric relaxation and 17O NMR spectroscopy. Water activity was also measured. Dielectric relaxation spectra indicate that all the polymer systems studied contained water exhibiting a dispersion at a frequency > 10(9) Hz; in other words, water with high mobility close to that of bulk water. The dielectric relaxation time of the highly mobile water increased as polymer concentration increased. The PVP- and gelatin-water systems also contained water exhibiting a dispersion at a frequency < 10(9) Hz, which can be considered to be "bound water" with a restricted mobility because of its association with polymer molecules. Dielectric relaxation spectroscopy was used to determine water mobility separately for the populations of highly mobile water and bound water, whereas NMR relaxation spectroscopy was used to determine the average mobility of both populations. The spin-lattice relaxation time of water in these polymer-water systems showed a deviation from the isotropic two-state model. Dielectric relaxation data indicate that this deviation can be ascribed to variations in the relaxation time of highly mobile water caused by a change in polymer concentration. The dielectric relaxation time of highly mobile water in the gelatin system did not change with a change in polymer concentration to the extent that it did in the PEG and PVP systems. This result is consistent with a slight change in water activity of the gelatin system with increasing polymer concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Chemical Phenomena↗
PubMed1979

Asynchronous ventricular relaxation: an angiographic temporal analysis of asynchronous left ventricular relaxation in man.

Segmental "early relaxation" is a common angiographic finding. An attempt was made to elucidate the temporal characteristics of this event. Twenty subjects with and 20 without segmental early relaxation were studied. The left ventricular diastolic relaxation time was precisely determined angiographically, and the findings were as follows: 0.12 +/- 0.04 second (mean +/- standard deviation) in the normal patients, 0.14 +/- 0.03 second in the patients with coronary artery disease but no segmental early relaxation and 0.20 +/- 0.04 second in the patients with segmental early relaxation. These findings indicate that early relaxation is associated with a significantly prolonged ventricular relaxation time. The use of the term asynchronous ventricular relaxation is proposed to denote the disturbed diastolic properties of the ventricle with "early relaxation."

Angiocardiography↗
PubMed1976

Protein rotational relaxation as studied by solvent 1H and 2H magnetic relaxation.

Earlier studies of the magnetic field dependence of the nuclear spin magnetic relaxation rate of solvent protons in solutions of diamagnetic proteins have indicated that this dependence (called relaxation dispersion) is related to the rotational Brownian motion of solute proteins. In essence, the dispersion is such that 1/T1 (the proton spin-lattice relaxation rate) decreases monotonically as the magnetic field is increased from a very low value (approximately 10 Oe); the dispersion has a point of inflection at a value of magnetic field which depends on protein size, shape, concentration, temperature, and solvent composition. The value of the proton Larmor precession frequency nu(c) at the inflection field appears to relate to tau (R), the rotational relaxation time of the protein molecules. We have measured proton relaxation dispersions for solutions of various proteins that span a three-decade range of molecular weights, and for one sample of transfer ribonucleic acid. We have also measured deuteron relaxation dispersions for solutions of three proteins: lysozyme, carbonmonoxyhemoglobin, and Helix pomatia hemocyanin with molecular weight 900 000. A quantitative relationship between both proton and deuteron dispersion data and protein rotational relaxation is confirmed, and the point is made that magnetic dispersion measurements are of very general applicability for measuring the rotational relaxation rate of macromolecules in solution. It has been previously shown that the influence of proton motion on the relaxation behavior of the solvent is not due to exchange of solvent molecules between the bulk solvent and a hydration region of the protein. In the present paper, we suggest that the interaction results from a long range hydrodynamic effect fundamental to the situation of large Brownian particles in an essentially continuum fluid. The general features of the proposed mechanism are indicated, but no theoretical computations are presented.

Deuterium↗
PubMed1992

Relationship between chronic hypoxia and in vitro pulmonary relaxation mediated by endothelium-derived relaxing factors in human chronic obstructive lung disease.

Endothelium-derived relaxing factors (EDRF) are paracrine vasodilator substances released by endothelial cells. There is compelling evidence to suggest that EDRF may play an important role in the modulation of vascular tone in the systemic circulation. However, the role of EDRF-mediated pulmonary relaxation in chronic lung disease is unknown. The authors have, therefore, investigated endothelium-dependent relaxation of isolated pulmonary arteries (PAs) obtained from 18 patients undergoing heart-lung transplantation for end-stage chronic hypoxic cor pulmonale (HCP). Control PAs were obtained from 10 patients, none of whom had evidence of HCP, and who underwent lobectomy for lung carcinoma. All vascular rings were studied immediately after lung excision. PA rings from control patients dose-dependently relaxed to cumulative doses of acetylcholine (ACh, 10(-10) to 10(-5) M), achieving a maximal relaxation of 73.2 +/- 4.4% from precontraction to phenylephrine. By contrast, PA rings from HCP patients achieved only 42.1 +/- 6.7% of maximal relaxation (p less than 0.01). Sodium nitroprusside (10(-4) M) relaxed all PA rings, with and without endothelium (carefully removed before study), obtained from both control and HCP patients. The endothelium-dependent maximal relaxation to ACh was positively related to pretransplant values of PaO2 (r = 0.59; p less than 0.01), but no relationship was found with either PaCO2 (r = -0.41) or FEV1 (r = -0.14). The authors conclude that pulmonary relaxation mediated by EDRF is impaired in human HCP and suggest that such impairment may be related to severity of the preexisting chronic hypoxemia.

Acetylcholine↗
PubMed2002

The effect of haemosiderosis and blood transfusions on the T2 relaxation time and 1/T2 relaxation rate of liver tissue.

Patients with chronic anaemia need repeated blood transfusions, which eventually lead to iron overload. The excess iron from blood transfusions is deposited in the reticuloendothelial system and in the parenchymal cells of the liver, spleen and other organs. Cellular damage is likely to occur when iron overload in the liver is pronounced. Liver biopsy is still necessary to evaluate the degree of haemosiderosis or haemochromatosis. To avoid this invasive procedure, methods have been sought to determine the concentration of iron in liver tissue and to estimate the effect of the treatment of haemosiderosis or haemochromatosis. In this MRI study, the T2 relaxation time and the 1/T2 relaxation rate of liver were determined in 23 patients who had undergone repeated blood transfusions for chronic anaemia. The first 60 transfusions had the greatest influence on the measured T2 relaxation time, with T2 relaxation time decreasing as haemosiderosis progresses. The 1/T2 relaxation rate increases significantly in a linear fashion when the number of blood transfusions increases up to 60. After 60 transfusions the influence of additional blood transfusions on the T2 value was minimal; the same response, although in reverse, was seen in the 1/T2 relaxation rate curve. One possible explanation for this may be that the MR system could detect the effect of only a limited amount of iron excess and any concentration over this limit gives a very short T2 relaxation time and a very weak signal from the liver, which is overwhelmed by background noise. However, in mild and moderate haemosiderosis caused by blood transfusions, T2 relaxation time and 1/T2 relaxation rate reflect iron accumulation in liver tissue.

Adipose Tissue↗
PubMed1988

Pharmacological evidence that endothelium-derived relaxing factor is nitric oxide: use of pyrogallol and superoxide dismutase to study endothelium-dependent and nitric oxide-elicited vascular smooth muscle relaxation.

The principal objective of this study was to elucidate the influence of superoxide anion on both endothelium-dependent arterial relaxation elicited by acetylcholine and endothelium-independent arterial relaxation produced by nitric oxide (NO). Pyrogallol was used to generate superoxide in the oxygenated bathing medium, and superoxide dismutase was used to scavenge superoxide. Pyrogallol caused endothelium-dependent contractions of bovine intrapulmonary arterial and venous smooth muscle after precontraction of muscle by phenylephrine. Acetylcholine- and NO-elicited arterial relaxations were promptly converted to marked contractions upon addition of pyrogallol. Moreover, pyrogallol markedly inhibited the development of arterial relaxant responses to acetylcholine and NO. However, isoproterenol- and glyceryl trinitrate-elicited arterial relaxations were unaffected by pyrogallol. Both pyrogallol and oxyhemoglobin enhanced arterial contractile responsiveness to phenylephrine in an endothelium-dependent manner, whereas indomethacin was without effect. Similarly, both pyrogallol and oxyhemoglobin inhibited acetylcholine- and NO-elicited arterial cyclic GMP accumulation, whereas indomethacin was without effect. Uncontracted arterial rings maintained under tension showed endothelium-dependent contraction and decreased cyclic GMP levels in response to oxyhemoglobin but not pyrogallol. Superoxide dismutase enhanced arterial relaxation and cyclic GMP accumulation in response to both acetylcholine and NO. Using a bioassay superfusion cascade system in which intact perfused artery was the source of endothelium-derived relaxing factor (EDRF) and three endothelium-denuded arterial strips mounted in series served as the detector of EDRF, superfusion of strips with pyrogallol blocked relaxation caused by perfusion of artery with acetylcholine. Superoxide dismutase enhance the relaxations produced by arterial perfusion with acetylcholine and prevented the effects of pyrogallol.

Animals↗
PubMed1985

Blockade of endothelium-dependent relaxation by the amiloride analog dichlorobenzamil: possible role of Na+/Ca++ exchange in the release of endothelium-derived relaxant factor.

The importance of extracellular calcium for the expression of endothelium-dependent relaxation was examined in isolated rat aortic rings contracted by methoxamine. The endothelium-dependent relaxation generated by acetylcholine or the calcium ionophore A23187 was eliminated when rings were placed in physiological buffer to which calcium had not been added. The endothelium-independent relaxation to sodium nitroprusside was still elicited in the presence of this "low calcium" buffer. Pretreatment of aortic rings with high concentrations of nifedipine (5 X 10(-7) M) or verapamil (10(-5) M) caused a comparable displacement to the right (2-3 times) in the relaxant dose-response curve for acetylcholine, A23187 and sodium nitroprusside with little or no changes in the maximal relaxation obtained with these vasodilators. Increasing concentrations of dichlorobenzamil, an analog of amiloride and a recently described inhibitor of calcium influx via sodium-calcium exchange, functionally antagonized and abolished the relaxations elicited by acetylcholine and A23187, but had no appreciable effect on the relaxations to sodium nitroprusside or atrial natriuretic factor (an endothelium-independent vasodilator). Similar results were obtained using isolated rabbit aortic rings. Thus, although the presence of extracellular calcium is critically required for the expression of endothelium-dependent relaxation, the associated calcium translocation is not blocked by the organic calcium entry blockers. The results with dichlorobenzamil suggest that sodium-calcium exchange may be an important mechanistic step in the release of endothelium-derived relaxant factor.

Acetylcholine↗